.png){kind=icon}
返回
Histone Methylation Regulates Memory Formation
.png){kind=icon}
OA
AI
DOI：10.1523/JNEUROSCI.3732-09.2010.png)
.png){kind=icon}
原文求助.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
It has been established that regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early step in the induction of synaptic plasticity and formation of long-term memory. In this study, we investigated the contribution of another histone modification, histone methylation, to memory formation in the adult hippocampus. We found that trimethylation of histone H3 at lysine 4 (H3K4), an active mark for transcription, is upregulated in hippocampus 1 h following contextual fear conditioning. In addition, we found that dimethylation of histone H3 at lysine 9 (H3K9), a molecular mark associated with transcriptional silencing, is increased 1 h after fear conditioning and decreased 24 h after context exposure alone and contextual fear conditioning. Trimethylated H3K4 levels returned to baseline levels at 24 h. We also found that mice deficient in the H3K4-specific histone methyltransferase, Mll, displayed deficits in contextual fear conditioning relative to wild-type animals. This suggests that histone methylation is required for proper long-term consolidation of contextual fear memories. Interestingly, inhibition of histone deacetylases (HDACs) with sodium butyrate (NaB) resulted in increased H3K4 trimethylation and decreased H3K9 dimethylation in hippocampus following contextual fear conditioning. Correspondingly, we found that fear learning triggered increases in H3K4 trimethylation at specific gene promoter regions (Zif268 and bdnf) with altered DNA methylation and MeCP2 DNA binding. Zif268 DNA methylation levels returned to baseline at 24 h. Together, these data demonstrate that histone methylation is actively regulated in the hippocampus and facilitates long-term memory formation.
Keyword:
LONG-TERM-MEMORY
BEHAVIORAL-TEST BATTERIES
TRANSCRIPTIONAL REPRESSION
EPIGENETIC MECHANISMS
CHROMATIN REGULATION
SYNAPTIC PLASTICITY
GENE-TRANSCRIPTION
PREFRONTAL CORTEX
DNA METHYLATION
CONTEXTUAL FEAR
期刊
IF:
4
论文数:
1.4K
被引数:
13.5W
机构
引用论文
Improved diagnosis of Pneumocystis carinii infection by polymerase chain reaction on induced sputum and blood.png)
The Lancet
The LancetIF0
PREAI
分享收藏分享收藏THE RECURRENCE OF WHOOPING COUGH: POSSIBLE IMPLICATIONS FOR ASSESSMENT OF VACCINE EFFICACYThe Lancet
The LancetIF0
PREAI
分享收藏Targeted recruitment of set1 histone methylase by elongating pol II provides a localized mark and memory of recent transcriptional activity通过延长pol II靶向募集set1组蛋白甲基化酶提供了最近转录活性的局部标记和记忆MOLECULAR CELL
OAAI
MOLECULAR CELLIF16.6
OAAI分享收藏Increased Frequency of Non-Insulin-Dependent Diabetes Mellitus Among Narcoleptic PatientsSleepOAAI
SleepIF0
OAAI分享收藏
查看更多内容